rs1476991

chr7-29480426-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004067.4(CHN2):c.654+70G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,483,598 control chromosomes in the GnomAD database, including 112,307 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (8860 hom., cov: 33)
  • Exomes 𝑓: 0.39 (103447 hom.)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

Genes affected

CHN2 (HGNC:1944): (chimerin 2) This gene encodes a guanosine triphosphate (GTP)-metabolizing protein that contains a phorbol-ester/diacylglycerol (DAG)-type zinc finger, a Rho-GAP domain, and an SH2 domain. The encoded protein translocates from the cytosol to the Golgi apparatus membrane upon binding by diacylglycerol (DAG). Activity of this protein is important in cell proliferation and migration, and expression changes in this gene have been detected in cancers. A mutation in this gene has also been associated with schizophrenia in men. Alternative transcript splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHN2	NM_004067.4	c.654+70G>A		intron_variant		ENST00000222792.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHN2	ENST00000222792.11	c.654+70G>A		intron_variant		1	NM_004067.4	P1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 50065 AN: 152048 Hom.: 8862 Cov.: 33

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.337

GnomAD4 exome AF: 0.392 AC: 521620 AN: 1331432 Hom.: 103447 AF XY: 0.394 AC XY: 262736 AN XY: 666560

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.314

Gnomad4 ASJ exome AF: 0.403

Gnomad4 EAS exome AF: 0.415

Gnomad4 SAS exome AF: 0.442

Gnomad4 FIN exome AF: 0.352

Gnomad4 NFE exome AF: 0.399

Gnomad4 OTH exome AF: 0.381

GnomAD4 genome AF: 0.329 AC: 50064 AN: 152166 Hom.: 8860 Cov.: 33 AF XY: 0.329 AC XY: 24438 AN XY: 74390

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.335

Alfa AF: 0.378 Hom.: 15390

Bravo AF: 0.321

Asia WGS AF: 0.378 AC: 1312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.020
Dann	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1476991; hg19: chr7-29520042;